Weizmann Institute scientists take us one step closer toward creating transplant organs – Photo: GettyImages

According to the Institute, and a report in the medical journal Nature, one of the obstacles to employing human embryonic stem cells for medical use lies in their very promise: They are born to rapidly differentiate into other cell types. Until now, scientists have not been able to efficiently keep embryonic stem cells in their pristine stem state. The alternative that has been proposed to embryonic stem cells — reprogrammed adult cells called induced pluripotent stem cells (iPS cells) — have similar limitations. Though these can differentiate into many different cell types, they retain signs of “priming” — commitment to specific cell lineages.

A team at the Weizmann Institute of Science has now taken a large step toward removing that obstacle by creating iPS cells that are completely “reset” to the earliest possible state and have maintained them in that state. Among other things, this research may, in the future, pave the way toward the ability to grow transplant organs to order, the Institute said.

Since they were first created in 2006, iPS cells have been touted as an ethical and practical substitute for embryonic stem cells. They are made by inserting four genes into the genomes of such adult cells as skin cells. This turns back the developmental clock almost all the way — but not completely — to an embryonic-stem-cell-like state.

Dr. Yaqub (Jacob) Hanna, principle investigator of the Weizmann Institute’s Molecular Genetics Department and his team’s breakthrough was in realizing that getting cells to revert into their near embryonic state was not enough. Maintaining the cells in the neutral “naive” state, before they differentiate into specific types of cells, was equally important. Hanna’s team developed a technique to preserve iPS cells in their “naive” state after observing the behavior of iPS cells in lab mice, which stayed in an undifferentiated state for much longer.

“These cells correspond to the earliest stages of human embryonic stem cells that have been isolated. We managed to freeze what is essentially a very fleeting situation and to produce a new, naïve, pluripotent state in stem cells.” Hanna said.

In an interview, Hanna said, “When we grow the cells in the petri dish we don’t know if they’re maintaining their original state as in the embryo. This is what’s new: this is the first time that we can keep the cells in what we call the ‘naive configuration.’

“In some ways you could call this regeneration of cells. As we age, chromosome length gets shorter. But here the chromosomes go back to their original, natural length. We can also inject these “naive” cells into a host mouse embryo. We can let the embryo develop and we can see that there is chimerism [merging of tissues from multiple species] with the mouse tissue.

“I think we can definitely say that we have found the fountain of youth,” the molecular biologist tells this reporter, in a deadpan voice. “And I think our work is really optimizing completely this fountain of youth. And where this is going now is how to control these cells, to differentiate between specific cell type with great control and flexibility from our side.

“Let’s say that from a patient, you want to make liver cells. The challenge for us now is how to take these ‘naive’ cells and in the petri dish make a liver. Or, from our study, it starts creating the possibility that with these cells you may consider growing organs in other species. We don’t know if that works. There are a lot of ethical issues to consider. But we’ve put this on the table,” Hanna said.

Hanna has dedicated most of his life, and especially the last five years, to this kind of research. The scientific field will decide whether or not his breakthrough is significant or not. “Science is a meritocracy. I think this is very important and I’m working on this very, very hard.”

Hanna’s paper has been published in Nature, an important scientific journal. He thinks his research will spawn many new questions and research directions.

“What we are looking at now is how are the cells better differentiated into different cell types, and perhaps this will solve many of the previous problems, with particular emphasis on making, for example, sperm or blood cells.

“I think others will try to translate what we do with human cells with other species, other primates such as monkeys. There, for instance, you’d want to be able to make engineered animals,” Hanna adds.

View original Israel Hayom publication at: http://www.israelhayom.com/site/newsletter_article.php?id=13013